DESCRIPTION (Applicant's Description) Advances in psychoneuroimmunology have provided clear and compelling evidence that stress leads to changes in immune function. Stress-induced immune modulation may influence the outcome and control of breast cancer. To understand the effect of stress on a woman's immune system and its relationship to breast cancer control, requires the evaluation of a naturalistic stress paradigm. Based on our preliminary studies, the experience of diagnostic breast biopsy provides such a stress paradigm. Our results show that the stress of impending breast biopsy leads to psychological stress, neuroendocrine activation, and a decrease in natural killer (NK) cell activity (NKCA). NK cells mediate natural resistance against tumor cells, and are particularly important in the control of tumor metastasis. The purpose of the proposed pilot study is to investigate potential mediators that may account for stress-induced reduction in NK cell activity. Cytokine activation is essential to optimal NK cell activity and the adrenocortical stress hormones, cortisol and dehydroepiandrostarons (DHEA), regulate the pattern of cytokine production. Therefore, the role of Thl/Th2 cytokines in the psycho-andocrine and NK cell response of women pro-and post-breast biopsy will be determined. The psychological response will be measured by assessing mood disturbance, perceived stress, and anxiety. Additionally, psychological constructs which may modify stress perception will be measured and include, resilience and sense of coherence. Stress-induced neuroendocrine activation and NK cell activity will be evaluated in the context of these psychological measures. A within groups design in which women experiencing heightened psychological stress and low NK cell activity (pre- biopsy) followed by alleviation of stress and restoration of NK cell activity (post-biopsy with benign results) will be used to follow patterns of Thl /Th2 cytokines and plasma levels of stress hormones. Potential differences in these responses in women with benign versus those with malignant breast biopsy findings will be determined. This study is unique in that it will provide an integrated psycho-endocrine-immune profile of women early in the cancer trajectory, as well as an understanding of the role of potential mediators of stress-induced immune depression. An understanding of the mechanisms underlying the stress-induced reduction of NKCA has considerable implications not only for women undergoing breast biopsy, but most importantly for the development and testing of interventions that can prevent and/or control NK cell depression in women diagnosed with breast cancer. Such intervention may improve the response to standard therapy, improve symptom management, and hence the quality of life of women with breast cancer.